Chemoprevention of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]-pyridine (PhIP)-induced mammary gland carcinogenesis by antioxidants in F344 female rats

Chemopreventive effects of the antioxidants 1-O-hexyl-2, 3,5-trimethylhydroquinone (HTHQ), 3-0-ethylascorbic acid (EAsA),3-O-dodecylcarbomethylascorbic acid (DAsA), green tea catechins(GTC) and ellagic acid on 2-amino- 1-methyl-6-phenylimidazo4,5-b]pyridine (PhIP)-induced mammary carcinogenesis were examinedin female F344 rats. Groups of 20–21 6-week-old rats weremaintained on a powdered diet containing 0.02% PhIP alone, PhIPtogether with 0.5% HTHQ, 1% EAsA, 1% DAsA, 1% GTC or 0.1% ellagicacid, these antioxidants alone or basal diet alone without supplementfor 52 weeks. The survival rates of PhIP plus antioxidant groupsat the end of the experiment were higher than that of the PhIPalone group. Sequential observation of palpable mammary tumorsdemonstrated only one tumor by week 52 in the PhIP plus HTHQgroup, whereas 40% of the rats receiving PhIP alone had tumorsby this time point. The final incidence of mammary adenocarcinomaswas significantly decreased in the PhIP plus HTHQ group (4.8%,P<0.01) as compared to the PhIP alone value (40%). Althoughstatistically not significant, incidences of adenocarcinomasin the other antioxidant-treated groups (23.8–28.6%) werealso lower than in the PhIP alone group. Furthermore, the incidenceof large intestinal tumors in the PhIP plus HTHQ group (0%)showed a tendency to decrease relative to the PhIP alone group(16.7%). These results indicate that antioxidants, particularlyHTHQ, exert a potent chemopreventive action against PhIP-inducedcarcinogenesis.